Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Alexithymia and its relationships with acute phase proteins and cytokine release: an updated review.

The alexithymia construct is multidimensional and comprises several features: (a) difficulty in identifying and describing feelings, (b) difficulty in distinguishing feelings from the bodily sensations, (c) diminution of fantasy, and (d) concrete and poorly introspective thinking. Altered immune responses have been seen in some psychiatric disorders and several data suggest that analogous changes could also be observable in alexithymia. Hence, the aim of this review is to investigate the relationships between alexithymia and acute phase proteins and cytokines in psychiatric, psychosomatic and medical diseases. Several studies have reported an association between alexithymia and higher circulating levels of acute phase proteins, especially C-Reactive Protein. Moreover, in alexithymic subjects the pro-inflammatory and anti-inflammatory cytokine balance may be tuned toward a pro-inflammatory imbalance with a concomitant altered cell-mediated immunity. These findings may be consistent with the "“stress-alexithymia hypothesis"”. Therefore, the screening of alexithymic traits and the administration of appropriate psychological and psychotherapeutical interventions should be integral parts of disease management programs. Supplying such interventions will probably help with prevention of the development of the disease and/or its exacerbation by improving the quality of life of alexithymic individuals.

Is there a role for agomelatine in the treatment of anxiety disorders?A review of published data.

Anxiety disorders (Ads) are the most common type of psychiatric disorders, Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.

Nerve growth factor and brain-derived neurotrophic factor concentrations in schizophrenia: a review.

There is growing interest in the role of neurotrophins in the pathophysiology of schizophrenia. Neurotrophins are a large family of dimeric polypeptides that promote the growth and the differentiation of developing neurons in the central and peripheral nervous systems as well as the survival of neuronal cells in response to stress. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations are here reviewed in relation to medication-naive early psychotic patients and in medicated chronic schizophrenic patients. Most data point to decreased plasma and serum NGF and BDNF concentrations in naive drug and in medicated schizophrenic patients compared to healthy controls. Higher BDNF levels were observed in patients with the paranoid subtype of schizophrenia. Low serum BDNF levels were associated with reduction in hippocampal volume (HV) at the onset of schizophrenia. Evidence on the correlation between BDNF levels and positive and negative schizophrenic symptoms were ambiguous. There are contrasting results on a possible correlation between increase in BDNF concentrations and treatment with antipsychotics. Antipsychotic treatment can elevate NGF values, specifically atypical. Growth factors might be good candidates as prognostically and diagnostically useful markers in schizophrenia.

Psychophysical distress and alexithymic traits in chronic fatigue syndrome with and without comorbid depression.

Patients with chronic fatigue syndrome (CFS) often report a comorbid depressive disorder. Comorbid depression may negatively influence the long-term outcome of CFS therefore it must be correctly diagnosed and treated. The aim of the present study is to provide a clinical and psychometric assessment of CFS patients with and without depressive features. A comparative analysis between 57 CFS subjects (CDC, 1994), 17 of whom with a comorbid depression, and 55 matched healthy volunteers was assessed to evaluate the presence of any psychophysical distress and alexithymic traits, by means of Symptom Checklist-90-R (SCL-90R) and Toronto Alexithymia Scale (TAS-20). The severity of fatigue was also assessed in all CFS patients using the Fatigue Impact Scale (FIS). With regard to psychiatric comorbidity, the SCL-90R scores showed higher levels of somatic complaints in CFS patients than in healthy subjects, whereas augmented depressive and obsessive-compulsive symptoms were observed only in the depressed CFS subgroup. When comparing the TAS-20 scores, we observed a selective impairment in the capacity to identify feelings and emotions, as measured by the Difficulty in Identifying Feelings subscale (DIF), non-depressed CFS patients showing an intermediate score between depressed CFS and healthy controls. Finally, in terms of FIS scores, a statistical trend versus a higher fatigue severity in depressed CFS patients, with respect to non-depressed ones, was observed. In conclusion, comorbid depression in CFS significantly increased the level of psychophysical distress and the severity of alexithymic traits. These findings suggest an urgent need to address and treat depressive disorders in the clinical care of CFS cases, to improve social functioning and quality of life in such patients.

Major depressive disorder, anhedonia and agomelatine: an open-label study.

Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.

Language proficiency and mental disorders among migrants: A systematic review.

BACKGROUND: In this review, we aimed to evaluate the association between language proficiency (LP) and the prevalence and severity of mental disorders in migrants. Secondarily, we aimed to consider whether sociodemographic and migration-related factors may affect the correlation between LP and mental disorders. METHODS: MEDLINE, PsycArticles, EMBASE, and PsycInfo were systematically searched in April 2020 to identify original studies reporting prevalence of psychiatric symptoms or disorders among migrants and taking into account linguistic factors. RESULTS: The search of electronic databases initially yielded 1,944 citations. Of the 197 full texts assessed for eligibility, 41 studies were selected for inclusion in the systematic review. Thirty-five of the papers included reported a significant negative association between low LP and prevalence and/or severity of psychiatric symptoms or disorders, whereas only two records found the opposite relationship and four papers reported no association between them. Inadequate LP was consistently associated with several mental disorders in migrants, including psychotic, mood, anxiety, and post-traumatic stress disorders. Notably, all the four longitudinal studies that met inclusion criteria for this review reported a positive effect of LP acquisition over time on prevalence or symptom severity of mental disorders. CONCLUSIONS: Even though larger prospective studies are needed to better evaluate the relationship between LP and psychiatric disorders among migrants, we believe that the present findings could be inspiring for authorities to provide support and courses to improve migrants' language proficiency upon arrival.

The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature.

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

"Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications.

In the early 1990s, several studies reported the misuse of codeine and promethazine hydrochloride cough syrup. Since then, the combination of this pharmaceutical, together with sprite or alcohol, known on the streets as "purple drank" or "lean", has become a popular drug among rap singers who promote its tranquilizing and euphoric effects through their music and videos. This review examines the "purple drank" phenomenon, taking into consideration its clinical and social implications. The study was conducted using PubMed, Scopus, and Web of Science as search engines, applying several inclusion and exclusion criteria and the string "Purple AND drank", resulting in 138 records. Seven papers that met our criteria were found. The risk of bias assessment, when applicable, was also considered, resulting in a low level of risk. Epidemiological data highlighted a heterogeneous diffusion of the misuse of this mixture, which is not exclusively linked to a specific type of user (African-American teenagers, athletes, and rappers), as previously reported in American newspapers and in the social media. New digital tools should be taken into consideration for further social and medical evaluations of this phenomenon.

Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone.

Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5-15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90-Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.

Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia.

Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3' enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80 percent; controls-68 percent). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2*2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A allele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-kB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3' IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected.

The role of cholesterol levels in mood disorders and suicide.

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

Augmenting pharmacotherapy with neuromodulation techniques for the treatment of bipolar disorder: a focus on the effects of mood stabilizers on cortical excitability.

Introduction: Mood stabilizers and antipsychotics have been demonstrated to be effective in Bipolar Disorder, with lithium as the gold standard. However, the presence of adverse events and treatment-resistance is still a relevant issue. To this respect, the use of brain stimulation techniques may be considered as an augmentation strategy, with both Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) having shown some level of efficacy in bipolar patients although clinical trials are still not sufficient to draw any conclusion. Areas covered: The authors have conducted a systematic review of the literature, in order to evaluate the role of mood stabilizers on neural activity and cortical excitability. Furthermore, the article reviews neuromodulation techniques and highlights the potential of integrating pharmacological first-line therapies with these techniques to treat BD patients. Expert opinion: The combination of neuromodulation techniques and available pharmacotherapies is a valuable opportunity which is not undermined by specific effects on cortical excitability and could improve BD patient outcome. Neurostimulation techniques may be considered safer than antidepressant treatments in BD, with a lower level of manic switches and may represent a new treatment strategy in BD depressive episodes.

Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics.

AIMS: Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability. METHODS: Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale. RESULTS: Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia. DISCUSSION: In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse.

[Workers with alcohol and drug addiction problems. Consensus Document of the Study Group on Hazardous Workers]. / Lavoratori con problemi di alcol e dipendenze. Documento di Consenso del gruppo La.R.A. (Lavoratori Rischiosi per gli Altri).

BACKGROUND: Italian Law 81/08 (so-called "Unified Text of Laws on Health and Safety at Work"), came into force on 15 May 2008 and incorporates provisions related to medical surveillance of drug and alcohol dependency at the workplace. OBJECTIVES: Occupational health traditionally addresses the issue of protection of worker from occupational hazards. The issue of protection of third parties from behaviour of workers resulting from drug and alcohol dependency implies an original methodological approach, involving full cooperation of employer, employees, and health and safety consultants. METHODS: A consensus development meeting was organized under the leadership of the Italian Study Group on Hazardous Workers (La.R.A. group). The meeting brought together physicians of different specialties, legal experts and bioethicists, labour and management policy-makers, to discuss the issue and define the research data available, the standards that were appropriate, and which policies were fair. RESULTS: The efficacy of medical surveillance, including workplace drug-testing, relies on a comprehensive policy, including written and verbal information on the use of alcohol and drugs on the job, training for supervisors and management, employee education, and employee assistance structures. Sample collection and testing should be carried out in accordance with standardized and tested procedures. Small businesses will need assistance, including development of model policies, setting up consortia for testing services and if necessary request for National Insurance benefits to reduce costs. CONCLUSIONS: The recently introduced Italian legislation on occupational safety and health closely resembles Finnish law since it consists of a "double channel" for workplace drug testing. At recruitment, the employer is entitled to ask a job applicant for a certificate of "Job fitness", including drug tests, that can be issued only by a public health institution, where the job applicant works on a well-defined set of tasks which require accuracy, trustworthiness, independent judgement or a very good reaction capacity. The employer may also refer the employee to the public health institution to obtain a certificate in the course of an employment contract when there is a legitimate suspicion that the employee is working while under the effects of drugs or alcohol or that the employee is a drug addict. After recruitment, the physician responsible for medical surveillance of workers (the so-called "Competent Physician") is entitled to perform drug tests on employees. The need for a test is decided by the health care professional, not by the employer, and only a general report on the health of the employee ("fit", fit with restrictions" or "unfit") may be given to the employer. Workers positive for drug tests will be referred to a public health institution for re-testing and treatment.

An update of safety of clinically used atypical antipsychotics.

INTRODUCTION: The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. AREAS COVERED: We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). EXPERT OPINION: A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

A prospective assessment of opiate addiction treatment protocols for inpatients with HIV-related syndromes.

A sample of 114 intravenous drug abusers hospitalized for HIV-spectrum diseases, was allowed to choose between methadone maintenance, partial or complete withdrawal as inpatient programs and was reassessed 4 days after discharge. One third of the patients had relapsed into heroin abuse. Rates of early relapse were significantly lower in the partial withdrawal group and higher in the methadone maintenance group. Patients with longer hospitalization and more severe HIV-related syndromes were particularly at risk of early relapse. Also, 45 former intravenous drug abusers were reassessed. Relapses were even more frequent than among active abusers, especially if the drug-free period before admission had been shorter than 1 year.

Ultradian variation of nerve growth factor plasma levels in healthy and schizophrenic subjects.

Some studies in animal models showed that several neurotrophins may be implicated in the regulation of light-dependent suprachiasmatic pacemaker and in other functions implicated in long-term memory acquisition during sleep. However, no data are known about the role played by NGF in ultradian regulation in humans. The aim of this study was to investigate whether or not there is a natural diurnal fluctuation during daytime in healthy and schizophrenic subjects with a normal light/dark cycle. In a sample of 33 subjects (10 male schizophrenics and 23 healthy subjects) an ELISA assay was used to study the ultradian NGF cycle in blood samples at 9.00, 13.00 and 20.00 hours. The study showed an ultradian rhythm of NGF in healthy subjects with a "V" trend: higher at 9:00 and 20:00 and lower at 13:00. We also show significant differences between male and female controls. No NGF ultradian rhythm among schizophrenic patients compared to healthy subjects was found. The results of this study lead to a rhythmic NGF regulation that appears altered in schizophrenics, where higher levels in the morning and lower levels in the evening were observed, compared to the controls, and support the hypothesis of a role played by NGF in schizophrenia.